Einleitung: Die Somatostatin-Rezeptorszintigraphie (SRS) besitzt einen festen Stellenwert in der Diagnostik von Patienten mit neuroendokrinen GEP-Tumoren. Allerdings ist je nach Tumorentität mit einem erheblichen Anteil falsch negativer Befunde der SRS zu rechnen. Wir untersuchten daher die Gastrin-Rezeptorszintigraphie (GRS) zusätzlich zur SRS, um den Wert dieser neuen szintigraphischen Methode bei der Detektion von Tumorläsionen bei Patienten mit neuroendokrinen GEP-Tumoren zu überprüfen.

BACKGROUND:Salivary gland dysfunction with xerostomia is a major clinical problem without a causal therapy in most cases. The development of an animal model for scintigraphic assessment of salivary gland function has great clinical relevance for the investigation of promising new diagnostic and therapeutic strategies for chronic salivary gland diseases. This study reports the first experiences with scintigraphic analyses of salivary gland function in a rat model.MATERIALS AND METHODS:Anatomical and scintigraphic studies were performed for topographic differentiation of major salivary glands of Wistar rats. (⁹⁹m)technetium pertechnetate salivary gland scanning was performed, appropriate regions of interest were determined and the gland-to-background ratio was examined for the evaluation of salivary gland function.RESULTS:The quantitative analysis of salivary gland scintigraphy revealed a reliable comparison of major salivary glands on both sides with the gland-to-background ratio ranging from 1.26 to 1.94 with an average of 1.51.CONCLUSION:This model seems to be appropriate for functional studies in an experimental setting.

The ability of integrated 18F-fluoro-deoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated. Visual interpretation, tumour maximum standardized uptake value (SUVmax), liver SUVmax and tumour/liver SUVmax ratios were correlated with the findings of CT, shift MRI and final diagnosis (based on biopsy or clinical/radiological follow-up). A total of 109 adrenal masses were found: 49 were malignant and 60 were benign on final diagnosis. A tumour/liver SUVmax ratio threshold of 1.0 was more accurate in differentiating the tumour type than tumour SUVmax or visual interpretation alone. Diagnostic accuracy of CT and shift MRI (92 − 97%) was similar to that for FDG PET/CT (94 − 97%). In conclusion, FDG PET/CT accurately characterizes adrenal tumours, with excellent sensitivity and specificity. Use of 1.0 as the threshold for the tumour/liver SUVmax ratio seems to be promising for distinguishing benign from malignant adrenal masses in cancer patients.

The diagnostic accuracy of infection scintigraphy with 99mTc-labelled monoclonal antibody Fab' fragments (sulesomab) was studied in patients with suspected total knee arthroplasty (TKA) infection. Images from 26 patients were evaluated by two independent readers and compared with a quantitative interpretation of time-activity courses. Microbiological examinations and joint aspiration results were used as reference standards. Histologically, aseptic TKA loosening occurred in two patients and severe, moderate or mild septic loosening in four, nine and 11 patients, respectively. Diagnostic accuracy for severe infection was 100% for both readers, whereas for moderate infection accuracy decreased by 12% and 12% for readers one and two, respectively. For mild infection a further decrease of approximately 61% and 52% occurred for readers one and two, respectively. Quantitative evaluation gave significantly better results over visual interpretation with a diagnostic accuracy of 100% for severe infection and decreased by only 10% and 15% in patients with moderate and mild infection, respectively. Quantitative evaluation of 99mTc-Fab' fragments is highly sensitive and specific for diagnostic imaging of infection in patients with septically-loosened TKA.

Nuclear medicine imaging is now well accepted for the localization of septic foci. But in patients the results of infection scintigraphy, radiology and ultrasound remain unsatisfactory in the diagnosis of fever of unknown origin (FUO). In contrast to septic infections, patients with FUO - mostly in elderly patients - tend to have such conditions as occult tumours, atypical pneumonia, hematoblastosis, malignant lymphomas. (18)F(Fluor-18)-Fluordeoxyglucose-PET ((18)F-FDG PET) has made it possible to localize symptomatically occult changes with a high diagnostic accuracy and to achieve differentiation between benign and malignant changes.

This study describes the physicobiological characterization of PEI- and PEG-PEI polyplexes containing partially 2'-OMe modified 25/27mer dicer substrate siRNAs (DsiRNAs) and their in vivo behavior regarding biodistribution and systemic bioavailability after pulmonary application as well as their ability to knock down gene expression in the lung. Biophysical characterization included circular dichroism of siRNA in polyplexes, condensation efficiency of polymers and in vitro stability. After in vivo application, biodistribution and kinetics of radiolabeled polyplexes were quantified and recorded over time in three-dimensional SPECT images and by end point scintillation counting. The influence on lung tissue and on the humoral and cellular immunosystem was investigated, and finally knockdown of endogenous gene expression in the lung was determined qualitatively. While all of the polymers used in our study were proven to effectively condense siRNA, stability of the complexes depended on the PEG grafting degree. Interestingly, PEI 25 kDa, which showed the least interaction with mucin or surfactant in vitro, performed poorly in vivo. Our nuclear imaging approach enabled us to follow biodistribution of the instilled nanocarriers over time and indicated that PEGylated nanocarriers are more suitable for lung application. While moderate proinflammatory effects were attributed to PEI25k-PEG(2k)(10) nanocarriers, none of the treatments caused histological abnormalities. Our preliminary in vivo knockdown experiment suggests that PEG-PEI/siRNA complexes are promising nanomedicines for pulmonary siRNA delivery. These results encouraged us to further investigate possible adverse effects and to quantify in vivo gene silencing in the lung after intratracheal instillation of PEG-PEI/siRNA complexes.

Active as well as passive immunization against beta-amlyoid (Aβ) has been proposed as a treatment to lower cerebral amyloid burden and stabilize cognitive decline in Alzheimer's disease (AD). To clarify the mechanism of action underlying passive immunization, the in vivo distribution (and sites of degradation) of peripherally administered radiolabeled human and mouse anti-Aβ antibodies were analyzed in a transgenic mouse model of AD. In APP23 mice, a model in which mutated human amyloid precursor protein is overexpressed, the biodistribution of intravenously applicated 111indium-conjugated affinity-purified human polyclonal autoantibodies (NAbs-Aβ) was compared to that of monoclonal anti-Aβ1–17 (6E10), anti-Aβ17–24 antibodies (4G8) and anti-CD-20 (Rituximab), a non-Aβ targeting control. Blood clearance half-lives were 50 ± 6 h for Rituximab, 20–30 h for NAbs-Aβ, 29 ± 5 h for 4G8 and 27 ± 3 h for 6E10. Blood activity was higher for 6E10 at 4 h as compared to 4G8, Rituximab and NAbs-Aβ. At the 96 h time point, Rituximab had the highest blood activity among the antibodies tested. As expected, all antibodies displayed hepatobiliary clearance. Additionally, NAbs-Aβ was excreted in the urinary tract. Liver and kidney uptake of NAbs-Aβ increased over time and was higher than in the monoclonal antibodies at 48 h/96 h. The brain-to-blood radioactivity ratio for NAbs-Aβ at later time points (>48 h) was higher than that of 6E10, 4G8 and Rituximab. In addition, the distribution varied, with highest values found in the hippocampus. Our data indicate a cerebral accumulation of human NAbs-Aβ in the APP23 model. Further studies with human immunoglobulins and particularly with those that recognize different Aβ-epitopes are required in order to delineate in more detail the mode of action of NAbs-Aβ.

ReO 4 − has similar kinetics regarding the sodium iodide symporter (NIS) to I− and TcO 4 − in NIS-expressing tissue. We investigated the therapeutic potential of 186ReO 4 − in NIS-transfected neuroendocrine tumour tissue.

Nuclear medicine imaging is now well accepted for the localization of septic foci. But in patients the results of infection scintigraphy, radiology and ultrasound remain unsatisfactory in the diagnosis of fever of unknown origin (FUO). In contrast to septic infections, patients with FUO - mostly in elderly patients - tend to have such conditions as occult tumours, atypical pneumonia, hematoblastosis, malignant lymphomas. (18)F(Fluor-18)-Fluordeoxyglucose-PET ((18)F-FDG PET) has made it possible to localize symptomatically occult changes with a high diagnostic accuracy and to achieve differentiation between benign and malignant changes.

Radioimmunotherapy in lymphoma is crossing the threshold to become a standard mode of treatment. Whereas in solid tumors in preclinical studies, radioimmunotherapy has proven to be superior to conventional chemotherapy, clinical success is still limited. The purpose of this brief review is to analyze recent developments in preclinical as well as clinical radioimmunotherapy of solid, CEA-expressing tumors. Advances in experimental radioimmunotherapy are characterized by the development of metastatic, rather than subcutaneous, tumor models in nude mice, which seem to reflect the actual clinical situation much more accurately. Furthermore, the recent development of strategies to reduce the renal accretion of antibody fragments and peptides enables the use of such smaller molecules for therapy, especially those also labeled with radiometals and other forms of intracellularly retained radionuclides. Recent developments in clinical radioimmunotherapy are characterized by a trend toward the treatment of small-volume and micrometastatic disease, as is the case, e.g., in adjuvant settings. Interestingly, despite dramatic differences in size, weight and percent-of-injected-dose-per-gram uptake values, only small differences between animal models and the actual patient situation exist with respect to activity concentrations (in mu Ci/gram) in the tumors and tissues. Because the activity concentration over time determines the radiation absorbed dose, and thus biological effects, we postulate that animal models should be able to predict actual clinical scenarios fairly well. These findings could be used as guidelines in the design of future preclinical, as well as clinical, trials.

Leukocyte activation is a property of systemic infection.In a previous animal experiment we could demonstrate, that granulocytes, which were already activated by the immune system, were more useful in the evaluation of scintigraphic imaging infection than non activated donor granulocytes.The purpose of the present study was to investigate the in vitro activation of isolated polymorphonuclear (PMN) donor leukocytes in the presence of various biological active modulators in rabbits with E. coli infection.Methods: In vitro, incubation of isolated leukocytes of non infected donors was performed with different immune stimulating modulators such as granulocyte-colony stimulating factor (G-CSF), proinflammatory cytokines (IL-8, IL-1 ) and bacterial products (fMLP) at 37 degrees C for 2 hrs.Afterwards, the different radiolabeled granulocyte preparations were studied in rabbits with an E. coli infection in the left calf muscle.The soft tissue infections were scintigraphically visualized following injection of 18 MBq 99m Tc-HMPAO-purified-heterologous in vitro stimulated granulocytes of non infected donor rabbits.Non-stimulated 99m Tc-HMPAO-purified-heterologous granulocytes served as a control.Gamma camera images were acquired at 2 min, 1, 2 and 4 hrs p.i.After the last image the rabbits were sacrificed and the uptake of the radiolabel in the dissected tissues was determined.Results: The 99m Tc-HMPAO-heterologous granulocytes incubated with G-CSF faintly visualized the infectious focus in the calf muscle at 2 hr p.i. and a slightly better delineation of the infection was noticed at 4 hr p.i.With heterologous granulocytes incubated with proinflammatory cytokines and fMLP a delineation of the infected calf muscle was not possible.The absolute uptake in the infected calf muscle was not significantly different between G-CSF (0.26 ± 0.06% ID), proinflammatory cytokines (0.23 ± 0.06% ID), fMLP (0.22 ± 0.02% ID) and the controls (0.17 ± 0.02% ID).The ratio of the infection to the non infected contralateral muscle was slightly higher for 99m Tc-HMPAO-heterologous granulocytes incubated with G-CSF (2.63 ± 0.03) as compared with the proinflammatory cytokines (1.3 ± 0.01), fMLP (1.4 ± 0.08) and the control (1.4 ± 0.04), respectively (all statistical differences were not significant with p=0.1-0.32). Conclusions:Our results confirm a direct, but probably weak stimulating effect of only G-CSF on the PMN for imaging infection.In addition, in-vivo heterologous granulocytes harvested from infected animals in a previous study showed better results as compared to the present data, suggesting the need of intrinsic cell activation for specific granulocyte migration, which cannot be mimicked by other stimuli.

Objective99mTc-tetrofosmin single photon emission computed tomography (SPECT) is routinely used in the evaluation of coronary artery disease. A variety of different tumors, however, also demonstrate 99mTc-tetrofosmin uptake. We report six patients found with unexpected mediastinal and thoracic tumor uptake during 99mTc-tetrofosmin myocardial perfusion scintigraphy (MPS). Materials and methodsWe investigated 2155 patients with 99mTc-tetrofosmin MPS during 2006–2007. One thousand four hundred and eighty-six of these patients had no coronary history and were sent to our department due to newly developed thoracic complaint such as chest pain, dyspnea and others. Six hundred and sixty-nine patients had coronary history. All patients underwent 99mTc-tetrofosmin exercise study. Patients with unexpected extracardiac 99mTc-tetrofosmin findings during MPS were referred to PET/CT for further diagnostic investigation. Region of interest (ROI; 99mTc-tetrofosmin) and SUVmax (2-[18F]fluoro-2-deoxy-D-glucose, 18F-FDG) were estimated and the results were compared with histological findings. ResultsAbnormal mediastinal and/or thoracic activities were visualized in six of the 2155 patients with 99mTc-tetrofosmin images. Subsequently, the patients underwent resection of a thymoma (n=2), nonsmall cell lung cancer (n=1) and breast cancer (n=3). In the patients with breast cancer one was a male patient with ductal, invasive breast cancer. Benign thymomas showed high 99mTc-tetrofosmin ROI >4.0 and low 18F-FDG SUVmax <2.0, whereas low 99mTc-tetrofosmin ROI <2.0 were found in nonsmall cell lung cancer and breast cancer and high 18F-FDG SUVmax >2.5 in these malignant tumors. ConclusionDuring 99mTc-tetrofosmin SPECT exercise stress tests performed in patients with suspected coronary artery disease, much more attention must be given to unexpected extracardiac uptakes. With 99mTc-tetrofosmin a large variety of different unknown tumors can be detected during MPS.

We present a patient with metastatic prostate cancer with known bone involvement and unknown osteomyelofibrosis.It has the general appearance of a superscan, with homogeneously increased tracer uptake and no visualization of the kidneys.However, while a superscan should have greater uptake in the axial skeleton compared to the appendicular skeleton, this scan is reverse, raising the suspicion of an overlying metabolic bone disorder.Subsequent laboratory-, bioptical findings confirmed a myeloproliferative syndrome with osteomyelofibrosis.As such, this scan demonstrates that in a patient with both affiliations, metabolic bone disease can override even severe osseous metastases on a bone scan.